The long term goal of this program is to optimize the application of hyperthermia (HT) as an adjuvant to radiotherapy (RT) and/or chemotherapy. Optimization of this treatment is dependent upon progress in five areas: l) development of more accurate and less invasive means to measure three dimensional non-uniform temperature distributions, 2) establishment of an accurate and quantifiable HT dosimetry that correlates with treatment outcome, 3) development of means to identify patients who are most likely to benefit from HT, 4) development of methods to enhance the therapeutic efficacy of HT and 3) development of equipment that is technically capable of achieving desired thermal doses, as established from dose effect studies. The central focus of the program is based on three clinical trials that will prospectively test the potential therapeutic advantage of high vs low HT doses when combined with RT. These trials represent the first prospective HT dose escalation trials to be performed, and if successful, they will establish a quantitative basis for HT dosimetry that could lead to better application of this treatment in all patients. Project I will test high vs low HT doses with RT for treatment of soft tissue sarcomas in pet dogs. Project II will evaluate methods to enhance HT sensitivity by acutely reducing intratumoral pH or by reducing tumor blood flow to allow for better heating. Project III contains all human protocols. Protocols in superficial tumors and soft tissue sarcomas will compare outcome in groups of patients who receive high or low HT doses in combination with RT. Another protocol will compare patient specific computer generated models of power deposition to determine best optimization schemes to achieve highest temperatures from annular phased array RF devices. The final protocol will continue Phase 1 testing of intraperitoneal cisplatin with regional HT for the treatment of advanced recurrent ovarian cancer. Project IV will employ full thermal modeling of actual patients as a means to reconstruct three dimensional temperature distributions and will model the influence of non-uniform temperature fields and micro environmental conditions on tumor cell survival after HT+RT. Project V will continue investigation of the potential of 31-P magnetic resonance spectroscopy, MR Perfusion Imaging and pO2 histography to predict and monitor human and canine tumor response to HT+RT. Support for these efforts will be provided by administrative, biostatistics, animal and engineering cores. Developmental efforts in the engineering core include the evaluation of MR chemical shift imaging for non-invasive thermometry and the engineering of new applicators for HT treatment of a variety of tumors.